virus – may be a gene. … Of course, the problem bristles with implications. It touches the biochemistry of the thymus type of nucleic acids which are known to constitute the major part of the chromosomes but have been thought to be alike regardless of origin and species. It touches genetics, enzyme chemistry, cell metabolism and carbohydrate synthesis etc.
But Avery would not have been Avery had he let his excitement continue, and he concluded with his usual self-deprecation:
It’s lots of fun to blow bubbles – but it’s wiser to prick them yourself before someone else tries to. So there’s the story Roy – right or wrong it’s been good fun and lots of work. … Talk it over with [your colleague] Goodpasture but don’t shout it around – until we’re quite sure or at least as sure as present method permits. It’s hazardous to go off half cocked – and embarrassing to have to retract later. I’m so tired and sleepy I’m afraid I have not made this very clear. But I want you to know – and sure you will see that I cannot well leave this problem until we’ve got convincing evidence. Then I look forward and hope we may all be together – God and the war permitting – and live out our days in peace.
And after signing off ‘with heaps and heaps of love’, Avery added a final postscript:
Good night – it’s long after mid-night and I have a busy day ahead. God bless us, one and all. Sleepy, well and happy –
17
*
By the autumn of 1943, Avery and McCarty were as certain as they could be that the transforming principle was composed of DNA, but Avery remained concerned that there might be some protein contaminants that were producing the effects. So he asked for advice from the protein chemists John Northrop and Wendell Stanley, and the Rockefeller biochemists Van Slyke and Max Bergmann. They all gave the same, unhelpful answer. There was no magic solution: Avery wanted to prove a negative, to show that his extract was completely free of proteins, and this was impossible. The only thing he could do was get as much evidence as possible, using a variety of techniques, and then publish. Interestingly, McCarty’s notes of their meeting with Bergmann reveal that the senior biochemist had similar doubts about the allegedly uniform nature of DNA to those expressed by Jack Schultz in 1941. According to McCarty’s notes, Bergmann felt that the previous certainties about nucleic acids were beginning to weaken:
In the light of present knowledge, the statement that all nucleic acids are the same regardless of the source from which they are derived is nonsense. If they are large polymeric compounds, there is an endless number of possible combinations all of which would possess the same elementary composition but would differ in chemical structure none the less. Nucleic acids hold too prominent a place in biology to be completely non-specific substances. The lack of evidence of any specificity associated with nucleic acids is only due to the fact that they have not been investigated sufficiently.
18
For two months Avery and McCarty wrote up their findings for publication, with Avery weighing every word and often using material from his reports to the Rockefeller Institute as his starting point. From the opening sentences, the article showed the context in which the study was carried out, and gave a hint of the implications of the main findings: ‘Biologists have long attempted by chemical means to induce in higher organisms predictable and specific changes which thereafter could be transmitted in series as hereditary characters.’ The results they presented were detailed, and their identification of the transforming principle as DNA was based on several strands of evidence – chemical composition; inactivation of the extract by enzymes or temperatures that affected DNA; no effect of enzymes that digested proteins; absence of immune reactions typical of those produced by proteins; responses to centrifugation,